Effects of pravastatin on mediators of vascular function in a mouse model of soluble Fms-like tyrosine kinase-1-induced preeclampsia

Karin A. Fox, Monica Longo, Esther Tamayo, Talar Kechichian, Egle Bytautiene, Gary D.V. Hankins, George R. Saade, Maged M. Costantine

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

OBJECTIVE: We sought to investigate the mechanisms of action by which pravastatin improves vascular reactivity in a mouse model of preeclampsia induced by overexpression of soluble Fms-like tyrosine kinase-1 (sFlt)-1. STUDY DESIGN: Pregnant CD-1 mice were randomly allocated to tail vein injection with adenovirus carrying sFlt-1 or murine immunoglobulin G2 Fc (control), and thereafter to receive pravastatin (5 mg/kg/d) or water. Mice were sacrificed at gestational day 18. Protein expression of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor receptor-1, and hemeoxygenase-1 were assayed by Western blot in aorta, liver, and kidneys. Serum total cholesterol concentrations were measured. RESULTS: Pravastatin up-regulated eNOS expression in the aorta of sFlt-1 mice by nearly 2-fold (P=.005) to levels similar to control mice. Total cholesterol levels, vascular endothelial growth factor receptor-1, and hemeoxygenase-1 protein expression were similar across groups. CONCLUSION: Pravastatin prevents vascular dysfunction in part by upregulation of eNOS in the vasculature. Our data support a role for statins in preeclampsia prevention.

Original languageEnglish (US)
Pages (from-to)366.e1-366.e5
JournalAmerican journal of obstetrics and gynecology
Volume205
Issue number4
DOIs
StatePublished - Oct 2011

Keywords

  • CD-1 mouse
  • Endothelial nitric oxide synthase
  • Pravastatin
  • Preeclampsia
  • Soluble Fms-like tyrosine kinase-1

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Fingerprint Dive into the research topics of 'Effects of pravastatin on mediators of vascular function in a mouse model of soluble Fms-like tyrosine kinase-1-induced preeclampsia'. Together they form a unique fingerprint.

  • Cite this